MODULATORY ACTION OF PROGESTERONE AND PROGESTERONE ANTAGONISTS ON HYPOTHALAMIC-PITUITARY FUNCTION

The ability of ovarian steroids to sensitize and desensitize the pitui tary gonadotroph to hypothalamic gonadotrophin-releasing hormone (GnRH ) is essential for their modulatory actions on gonadotrophin secretion . The time-dependent actions of progesterone on GnRH-stimulated gonado trophin secretion from cultured pituitary cells obtained from female r ats were examined. Progesterone induced an acute stimulatory effect on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secre tion in cell perifusion studies, from as early as 50 min after the ons et of progesterone treatment. Long-term incubation (52 h) of pituitary cells in static culture reduced the responsiveness of the gonadotroph to GnRH. The antiprogestins RU486, ZK 98.299, and ZK 98.734 blocked b oth the acute facilitatory and the long-term inhibitory action of prog esterone. In the absence of progesterone, the antiprogestins per se in duced marked inhibitory and stimulatory effects on GnRH-stimulated LH secretion. In brief, short-term treatment of non-oestrogen-primed cell s with antiprogestins was ineffective (ZK compounds) or reduced LH sec retion (RU486), while long-term treatment was stimulatory. Oestrogen-p rimed cells exerted exclusively inhibitory effects on GnRH-induced LH secretion. In conclusion, antiprogestins are effective antagonists of progesterone actions in the gonadotroph. However, they exert diverse a ctions on gonadotrophin secretion in the absence of progesterone, whic h might interfere with their antagonistic properties.